Background: Hepatitis C virus (HCV) causes acute and chronic human hepatitis infections. Due to the high genetic diversity and high rates of mutations in the genetic material so far there is no approved vaccine against HCV.

Materials and Methods: The aim of this study was to determination B and T cell conserved epitopes of E1 and E2 proteins from HCV and construction of a chimeric peptide as a novel epitope based vaccine for cross-protection against the virus. For this, one B and T-cell epitope from both E1 and E2 which was predicted by EPMLR and Propred-1 server and had the highest score and antigenicity in VaxiJen 2.0 and PAP servers were selected for construction of chimeric protein as a multi-epitope vaccine.

Results: The results of this study showed that the chimeric peptide had high antigenicity score and stability.Results also showed that most epitopes of E1 were located in two spectra consist of (45-65,88-107 and 148-182) while the results about B-cell epitopes of E2 showed that this protein had much less epitope than E1. The most epitope predicted for E2 were located in (12-24 and 35-54) spectra

Conclusion: In conclusion, epitope based vaccine which was designed by immunoinformatics methods could be considered as a novel and effective vaccine for cross-protection against HCV infection.